1. Field of Invention
The current invention relates to automated systems utilizing detection methods, and more particularly to an automated system operable to detect abnormalities of the eye.
2. Discussion of Related Art
The contents of all references, including articles, published patent applications and patents referred to anywhere in this specification are hereby incorporated by reference.
Age-related macular degeneration (AMD) is a disease of the retina that occurs mainly within the population over 50 and is the leading cause of blindness in this age group. Additional detail on the eye can be found in Hogan, et al., Histology of the Human Eye, W. B. Sanders, Philadelphia 1971. AMD has two manifestations, dry and wet (non-neovascular and neovascular). The dry form is the most prevalent and found in about 80% of the cases and can be further divided into an intermediate stage (the most prevalent dry form) and an advanced dry stage (atrophy of the retina, usually causing vision loss when involving the center of the retina). The intermediate stage of AMD is not accompanied by symptoms of vision loss. However, a defining asymptomatic sign indicating the onset of AMD is the presence of small accumulations of extracellular material in the retina called drusen. Drusen were first described in Donders, Beitrage zur pathologischen Anatomic des Auges. Archiv Für Ophthalmologic 1854, 1:106-18. Drusen form typically in the macula (the center of the retina) and represent a thickening of Bruch's membrane, just external to the outer layers of the retina and just internal to the vascular choroid of the eye. Small drusen are not uncommon at age 40 or 50 but large drusen are typically indicative of AMD. The mechanism for the formation of drusen and the way they lead to vision loss from atrophy of the wet form of AMD is not completely understood but one explanation is that their presence interferes with the supply of nutrients and oxygen to rods and cones.
The wet form of AMD, also considered an advanced stage of AMD because it typically leads to vision loss, is always preceded by drusen (the intermediate stage of AMD), although not necessarily by atrophy (the dry form of AMD and considered an advanced dry form when involving the center of the retina). The greater the area of drusen present in an eye, the greater chance the eye will progress to the advanced stage of AMD (either the dry atrophic form or the wet form or both). The wet form is manifested by the abnormal development of fragile blood vessels which often leak fluid or blood into or under the retina and are accompanied by ingrowth of scar tissue. It is the dysfunction of the retina from blood and fluid leaking from these vessels in the macula, along with loss of retina from atrophy or ingrowth of scar that eventually affects central vision needed for reading or driving, usually leaving peripheral vision intact. This is particularly significant since high resolution foveal vision is essential for basic occulomotor tasks such as fixation and saccading and to higher level vision tasks such as face recognition. Unfortunately, about 50% of people who develop the wet form in one eye will develop the wet form in the other eye within 5 years, so that wet AMD frequently leads to functional blindness. The prevalence of drusen is so common (approximately 8,000,000 people in the U.S. over the age of 50 with at least one eye having the intermediate stage of AMD), and the incidence of the wet form among those with the intermediate stage of AMD is so frequent (approximately 150,000 individuals each year among those with the intermediate stage) that AMD, left untreated, is the leading cause of blindness in people over the age of 50 in the United States and throughout much of the world. Wet AMD has several treatments: recently several anti-vascular endothelial growth factor (VEGF) therapy drugs have been FDA approved for injection into the eye to block the development of these vessels; use of at least one of these (ranibizumab), if applied before substantial loss has occurred, can reduce the incidence of legal blindness by about 75%.
While the intermediate stage of AMD is asymptomatic until atrophy affects the central macula or until the wet form develops, the advanced stage (the central atrophic dry form or the wet form) can cause severe vision loss and is expected to affect up to 3 million individuals in the US by 2020. The anti-VEGF therapies can prevent blindness in most cases provided the disease is detected and treated when progressing from the asymptomatic intermediate stage to the wet stage. It is essential to initiate these therapies before substantial vision loss has occurred so as to avoid functional blindness. This strategy requires an individual to know that he or she has the usually asymptomatic intermediate stage of AMD so that periodic self-monitoring and professional monitoring can occur to detect the onset of the wet stage, and so that these individuals will be educated as to how and where to seek prompt treatment if the wet form of AMD develops. In addition, there is some evidence to suggest that taking a dietary supplement such as that used in a government-sponsored study can reduce the risk of progression to the advanced stage in individuals who have the intermediate stage. Currently, detection methods such as ophthalmoscopy and clinical evaluation of fundus photographs by skilled specialists still remain the gold standard, but involve a completely manual and time consuming diagnostic workflow.
To perform a fundus examination it may be necessary to use an instrument to view and photograph the fundus of a patient's eye. For example, one such instrument in wide use is a fundus camera. FIG. 1 is an example of a conventional fundus camera 100. The fundus camera 100 is one example of an optical system to observe the fundus 102 of a subject's eye 104. The fundus camera 100 has an illumination path 106 and a viewing path 108. A constant illumination may be provided by an incandescence light bulb 110, for example. A brighter flash illumination may be provided by flash bulb 112 for use in conjunction with film-based cameras. Furthermore, the viewing path 108 may be split into a path for direct viewing 114 by a user and a path 116 to a camera 118 for photographing an image of the fundus 102 of the subject's eye 104. The beam splitter 120 may be replaced with a movable mirror 122 in some fundus cameras. The commercial fundus camera 100 is shown as an example and not meant to limit the scope of the current invention.
With the large baby-boom generation moving into its senior years, there is a real possibility that the relatively limited supply of clinicians may be unable to administer the necessary fundus examinations that are required for detection in a timely manner. Because of this, there is an important need for developing automated tools that can detect the intermediate stage AMD accurately and as a result allow for early education, intervention, and treatment of the wet form.
Furthermore, there is a need for automated algorithms that assist in subsequent tracking of the disease progression, which could help clinicians perform longitudinal studies and assess the effectiveness of various therapies aimed at reducing the development of progression of the intermediate stage.